Triazole derivatives as SCD inhibitors

1. A compound of formula (I):

wherein:

X represents —CONH—, —NHCO— or —CH 2 NH—;

R 1 represents:

—C 6-10 aryl optionally substituted by one, two or three groups independently selected from:

—C 1-3 alkyl, —C 1-6 alkoxy, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —OC 3-6 cycloalkyl or halogen;

R 2 represents hydrogen, —C 1-6 alkyl or —C 1-3 alkylOC 1-3 alkyl;

R 3 represents:

—C 5-9 heteroaryl optionally substituted by one, two or three groups independently selected from: —C 1-3 alkyl, —C 1-6 alkoxy, —CO 2 R 4 , —C(═O)NR 5 R 6 , —C(═O)NHC 1-3 alkylNR 7 R 8 , —C(═O)NHC 1-3 alkylOC 1-3 alkyl, —C(═O)NHC 1-3 alkylOH, —C(═O)R 9 , —C 1-6 alkylOH, —C(═O), —CHO, —C 1-3 alkylCO 2 C 1-3 alkyl, —C 1-3 alkylOC 1-3 alkyl, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —OC 3-6 cycloalkyl, —C 3-6 cycloalkyl or halogen;

R 4 represents —H or —C 1-3 alkyl;

R 5 represents —H or —C 1-3 alkyl;

R 6 represents —H or —C 1-6 alkyl;

R 7 represents —H or —C 1-3 alkyl;

R 8 represents —H or —C 1-3 alkyl; and

R 9 represents —C 6 heterocycle which is optionally substituted by a group independently selected from: —C 1-6 alkyl;

or a pharmaceutically acceptable salt thereof,

with the proviso that the compound of formula (I) is not

N-1,3-benzodioxol-5-yl-1-[(4-fluorophenyl)methyl]-1H-1,2,3-triazole-4-carboxamide

or N-(6-acetyl-1,3-benzodioxol-5-yl)-1-[(4-methylphenyl)methyl]-1H-1,2,3-triazole-4-carboxamide

and further provided that R3 is not an optionally substituted tetrahydronapthyridine when X is —NHCO or —CONH.

2. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein X represents —CONH—.

3. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein R 1 represents phenyl substituted by two groups independently selected from halogen.

4. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein R 2 represents hydrogen or —C 1-3 alkyl.

5. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein R 3 represents —C 5 heteroaryl containing 5 ring-atoms 1, 2, 3 or 4 of which are hetero-atoms independently selected from nitrogen, oxygen or sulphur and the remaining ring-atoms are carbon, optionally substituted by one, two or three groups independently selected from: —C 1-3 alkyl, —C 1-6 alkoxy, —CO 2 R 4 , —C(═O)NR 5 R 6 , —C(═O)NHC 1-3 alkylNR 7 R 8 , —C(═O)NHC 1-3 alkylOC 1-3 alkyl, —C(═O)NHC 1-3 alkylOH, —C(═O)R 9 , —C 1-6 alkylOH, —C(═O), —CHO, —C 1-3 alkylCO 2 C 1-3 alkyl, —C 1-3 alkylOC 1-3 alkyl, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —OC 3-6 cycloalkyl, —C 3-6 cycloalkyl or halogen.

6. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein R 3 represents —C 9 heteroaryl containing 9 ring-atoms 1, 2, 3 or 4 of which are hetero-atoms independently selected from nitrogen or sulphur and the remaining ring-atoms are carbon, optionally substituted by one, two or three groups independently selected from: —C 1-3 alkyl, —C 1-6 alkoxy, —CO 2 R 4 , —C(═O)NR 5 R 6 , —C(═O)NHC 1-3 alkylNR 7 R 8 , —C(═O)NHC 1-3 alkylOC 1-3 alkyl, —C(═O)NHC 1-3 alkylOH, —C(═O)R 9 , —C 1-6 alkylOH, —C(═O), —CHO, —C 1-3 alkylCO 2 C 1-3 alkyl, —C 1-3 alkylOC 1-3 alkyl, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —OC 3-6 cycloalkyl, —C 3-6 cycloalkyl or halogen.

7. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein R 3 represents —C 6 heteroaryl optionally substituted by one, two or three groups independently selected from: —C 1-3 alkyl, —C 1-6 alkoxy, —CO 2 R 4 , —C(═O)NR 5 R 6 , —C(═O)NHC 1-3 alkylNR 7 R 8 , —C(═O)NHC 1-3 alkylOC 1-3 alkyl, —C(═O)NHC 1-3 alkylOH, —C(═O)R 9 , —C 1-6 alkylOH, —C(═O), —CHO, —C 1-3 alkylCO 2 C 1-3 alkyl, —C 1-3 alkylOC 1-3 alkyl, —C 1-6 haloalkyl, —OC 1-6 haloalkyl, —OC 3-6 cycloalkyl, —C 3-6 cycloalkyl or halogen.

8. A compound of formula (I) according to claim 1 selected from:

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-[6-(methyloxy)-1,3-benzothiazol-2-yl]-1H-1,2,3-triazole-4-carboxamide,

Ethyl 2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-methyl-1,3-thiazole-5-carboxylate,

Ethyl 5-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-1,3,4-thiadiazole-2-carboxylate,

Methyl 2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-1,3-thiazole-5-carboxylate,

1-[(3,4-Dichlorophenyl)methyl]-N-(5-formyl-1,3-thiazol-2-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-{5-[(methyloxy)methyl]-1,3,4-thiadiazol-2-yl}-1H-1,2,3-triazole-4-carboxamide,

Methyl {2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-1,3-thiazol-4-yl}acetate,

Ethyl 2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-(trifluoromethyl)-1,3-thiazole-5-carboxylate,

1-[(3,4-Dichlorophenyl)methyl]-N-(4,5-dimethyl-1,3-thiazol-2-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Ethyl 2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-1,3-benzothiazole-6-carboxylate,

Ethyl {2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-5-methyl-1,3-thiazol-4-yl}acetate,

1-[(3,4-Dichlorophenyl)methyl]-N-(5,7-dioxo-4,5,6,7-tetrahydro[1,3]thiazolo[4,5-d]pyrimidin-2-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide,

Methyl 6-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-3-pyridinecarboxylate,

Methyl 2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-pyridinecarboxylate,

2-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-4-methyl-1,3-thiazole-5-carboxylic acid,

2-[({1-[(3,4-dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-1,3-oxazole-5-carboxylic acid,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-{4-methyl-5-[(methylamino)carbonyl]-1,3-thiazol-2-yl}-1H-1,2,3-triazole-4-carboxamide, (example 18)

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-(4-methyl-5-{[(3-methylbutyl)amino]carbonyl}-1,3-thiazol-2-yl)-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-(4-methyl-5-{[(1-methylethyl)amino]carbonyl}-1,3-thiazol-2-yl)-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-{5-[(ethylamino)carbonyl]-4-methyl-1,3-thiazol-2-yl}-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[5-({[2-(dimethylamino)ethyl]amino}carbonyl)-4-methyl-1,3-thiazol-2-yl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-(5-{[(3-methylbutyl)amino]carbonyl}-1,3-thiazol-2-yl)-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-[4-methyl-5-(4-morpholinylcarbonyl)-1,3-thiazol-2-yl]-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-{4-methyl-5-[(4-methyl-1-piperazinyl)carbonyl]-1,3-thiazol-2-yl}-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-[4-methyl-5-({[2-(methyloxy)ethyl]amino}carbonyl)-1,3-thiazol-2-yl]-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-(5-{[(2-hydroxyethyl)amino]carbonyl}-4-methyl-1,3-thiazol-2-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-{5-[(dimethylamino)carbonyl]-4-methyl-1,3-thiazol-2-yl}-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-{5-[(methylamino)carbonyl]-1,3-thiazol-2-yl}-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-{5-[(dimethylamino)carbonyl]-1,3-thiazol-2-yl}-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-(5-{[(2-hydroxyethyl)amino]carbonyl}-1,3-thiazol-2-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide,

2-[({1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}carbonyl)amino]-N-methyl-4-pyridinecarboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-{5-[(ethylamino)carbonyl]-4-methyl-1,3-thiazol-2-yl}-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-{4-methyl-5-[(methylamino)carbonyl]-1,3-thiazol-2-yl}-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-(5-{[(2-hydroxyethyl)amino]carbonyl}-1,3-thiazol-2-yl)-1H-1,2,3-triazole-4-carboxamide,

N-[5-(Aminocarbonyl)-1,3-thiazol-2-yl]-1-[(3,4-dichlorophenyl)methyl]-1H-1,2,3-triazole-4-carboxamide,

N-[5-(Aminocarbonyl)-4-methyl-1,3-thiazol-2-yl]-1-[(3,4-dichlorophenyl)methyl]-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-5-methyl-N-1,3,4-thiadiazol-2-yl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[5-(hydroxymethyl)-1,3-thiazol-2-yl]-5-[(methyloxy)methyl]-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[5-(hydroxymethyl)-4-methyl-1,3-thiazol-2-yl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[5-(hydroxymethyl)-1,3,4-thiadiazol-2-yl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-(2-hydroxyethyl)-1,3-thiazol-2-yl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

1-[(3,4-Dichlorophenyl)methyl]-N-[4-(hydroxymethyl)-2-pyridinyl]-5-methyl-1H-1,2,3-triazole-4-carboxamide,

N-{1-[(3,4-Dichlorophenyl)methyl]-5-methyl-1H-1,2,3-triazol-4-yl}-6-(methyloxy)-1,3-benzothiazole-2-carboxamide, or

{2-[({1-[(3,4-Dichlorophenyl)methyl]-1H-1,2,3-triazol-4-yl}methyl)amino]-1,3-thiazol-5-yl}methanol,

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 and at least one pharmaceutical carrier and/or excipient.

10. A pharmaceutical composition comprising a compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 8 and at least one pharmaceutical carrier and/or excipient.

11. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein X represents —NHCO—.

12. A compound of formula (I) or pharmaceutically acceptable salt thereof according to claim 1 wherein X represents —CH 2 NH—.

13. A compound according to claim 1 wherein the C 5-9 heteroaryl is a monocyclic or bicyclic ring system including an aromatic cyclic group containing 5 to 9 ring-atoms 1, 2, 3 or 4 of which are hetero-atoms independently selected from nitrogen, oxygen and sulphur and the remaining ring-atoms are carbon.

14. A compound according to claim 13 wherein the bicyclic structure contains at least one ring which is aromatic.

15. A compound according to claim 1 wherein the C 5-9 heteroaryl is an isoxazole, oxazole, thiazolopyrimidine, imidazole, thiazole, benzothiazole, thiadiazole, oxadiazole or pyridine.

16. A compound according to claim 1 wherein the C 5-9 heteroaryl is a thiazole, benzothiazole, thiadiazole, oxazole, pyridine or thiazolopyrimidine.